Context NK cells have an important role in innate immunity and in the regulation of immune response. The role of NK cells expressing the PD-1 regulatory receptor has not been explored in patients with autoimmune thyroid disease (AITD). Purpose To analyze the levels and function of PD-1 + NK cells in samples from AITD patients. Design Cases and controls, observational study. Setting Hospital Universitario la Princesa, Spain. Patients Forty patients with AITD, sixteen with Hashimoto thyroiditis (HT) and twenty-four with Graves’ disease (GD), and fifteen healthy controls. Intervention Multi-parametric flow cytometry analysis of peripheral blood NK cells. In vitro assays of cytotoxic activity of NK cells, and synthesis of cytokines. Main outcome measures. Levels and function of PD-1 + NK cells in blood samples from AITD patients and controls. Results Increased levels of NK cells and the CD56 dimPD-1 + subset were observed in GD patients. In HT, an enhanced expression of the regulatory receptors NKG2A and NKG2C by CD56 brightPD-1 + NK cells was detected. AITD patients showed an increased synthesis of IL-10 by CD56 brightPD-1 - NK cells, whereas CD56 dimPD-1 + cells from GD patients exhibited an enhanced production of IFN-γ. PD-1 + NK cells from patients with GD and HT showed an increased cytotoxic activity. Significant associations were observed in patients with GD or HT between the levels of PD-1 + NK cells and clinical laboratory parameters. Conclusions The different abnormalities in NK cell subset levels, in the expression of PD-1 and its function in AITD patients’ further support the complex role of these cells in this pathogenesis.

A low-grade inflammatory phenomenon is a feature of overweight and metabolic syndrome. The involvement of a pro-inflammatory Th17 lymphocyte subset and the CD69 + T regulatory (Treg) cell subtype in patients with metabolic dysfunction associated or not to overweight has not been fully elucidated. The aim of this study was to perform a quantitative and functional analysis of pathogenic Th17 lymphocytes and CD69 + Treg cells in patients with metabolic dysfunction (insulin resistance and dyslipidemia). The number of pathogenic Th17 cells and the levels and function of CD69 + Treg cells were analyzed in blood samples from individuals with metabolic dysfunction, associated or not to overweight. Pathogenic and non-pathogenic Th17 lymphocytes as well as Th22 cells were determined by eight-color flow cytometry analysis, whereas the levels and the suppressive function of CD69 + Treg cells were also analyzed by multiparametric flow cytometry. We detected increased levels of pro-inflammatory Th17 pathogenic cells and Th22 lymphocytes in overweight unhealthy individuals (p<0.001, compared to normal weight healthy). Conversely, diminished numbers of CD69 + Treg lymphocytes were observed in metabolically unhealthy individuals, with or without overweight. Likewise, the immunosuppressive function of CD69 + Treg cells was also defective in these patients. The increased levels of pathogenic Th17 cells along with a diminished number and function of CD69 + Treg lymphocytes may significantly contribute to the low-grade inflammatory phenomenon of metabolically unhealthy patients.

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